WO 01/60805 (SmithKline Beecham plc) discloses a novel class of pyrimidinone compounds, inter alia those substituted at N1.
The pyrimidinone compounds described in WO 01/60805 are inhibitors of the enzyme lipoprotein associated phospholipase A2 (Lp-PLA2) and as such are expected to be of use in therapy, in particular in the primary and secondary prevention of acute coronary events, for instance those caused by atherosclerosis, including peripheral vascular atherosclerosis and cerebrovascular atherosclerosis.
Several processes for the preparation of such pyrimidinone compounds are also disclosed in WO 01/60805, inter alia alkylation of the pyrimidinone nucleus. This process generally suffers from moderate yields due to the poor selectivity seen in the alkylation of the pyrimidinone nucleus. Preparation of such compounds is also disclosed in WO 03/16287. While this process achieves improved selectivity, it generally suffers from modest yield particularly in the disclosed regioselective step.
The present invention provides particularly advantageous processes, not hitherto disclosed, for the preparation of some of the pyrimidinone compounds disclosed in WO 01/60805.